Neuroprotective effects of microRNA 124 in Parkinson's disease mice

Arch Gerontol Geriatr. 2022 Mar-Apr:99:104588. doi: 10.1016/j.archger.2021.104588. Epub 2021 Nov 28.

Abstract

Background: Recent studies have revealed the close correlation between microRNAs (miRs) and Parkinson's disease (PD). Here, we aimed to investigate the neuroprotective effect of miR-124 in a PD mouse model.

Methods: MiR-124 expression in human plasma was detected by qRT-PCR. PD mouse model was established by stereotactic injection of 6-hydroxydopmine. Lentivirus were used to deliver and overexpress miR-124 and Axin1 into the substantia nigra. Multiple behavioral tests and oxidative stress assays were carried out to access the protective effect of miR-124 against PD. Western blot and luciferase assay were conducted to dissect the underlying molecular mechanisms.

Results: MiR-124 expression was decreased in PD patients. Overexpression of miR-124 in PD mice could improve motor defects, ameliorate dopaminergic neurons loss, and reduce oxidative stress. Mechanistically, miR-124 targeted Axin1 directly, and then attenuated PD progression via suppressing Axin1 and activating the Wnt/β-catenin pathways in PD mice.

Conclusion: MiR-124 is an important neuroprotective factor, which suppresses Axin1 and activates Wnt/β-catenin signaling pathways in PD mice.

Keywords: Axin1; Dopaminergic neurons; PD; Wnt/β-catenin; miR-124.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dopaminergic Neurons / metabolism
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs* / genetics
  • Neuroprotective Agents* / metabolism
  • Parkinson Disease* / genetics
  • Wnt Signaling Pathway / genetics

Substances

  • MIRN124 microRNA, human
  • MicroRNAs
  • Mirn124 microRNA, mouse
  • Neuroprotective Agents